The pharmacokinetic profile of RS-8359.
RS-8359 is very rapidly absorbed, metabolized and distributed following oral dosing, with significant concentrations of both parent drug and its principal metabolite appearing in plasma within 15 min. Plasma levels were linearly related to doses of up to 300 mg, beyond which absorption was diminished, perhaps due to a saturation effect. Clearance of RS-8359 is mainly through the renal system as the metabolite, and is virtually complete within 24 h. The kinetic profile of the drug best fits a two-compartment model, and mean residence time and half-life (beta) of the drug support a twice a day regimen for extended use. During multiple dosing twice a day for up to 6 weeks, steady state plasma drug levels were achieved within 48 h and there was no evidence of significant accumulation.
Püchler
K
K
Sankyo Europe GmbH, Düsseldorf, Germany.
Sasahara
K
K
Plenker
A
A
Nitanai
T
T
Witte
P U
PU
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; D011743:Pyrimidines; C059590:RS 8359